From a convenience perspective, many knee osteoarthritis (OA) studies have focused on those with moderate to severe disease because the natural history of OA occurs over years. Studying the disease earlier on is more challenging but this may be the timeframe in which an effective intervention can be implemented. Therefore, our interest is in those without disease or with early knee OA. When structures required to accommodate loading are compromised, knee OA occurs. Three domains of potentially modifiable risk factors that may contribute to the health of these load distributing structures include: physical activity, cardiovascular risk factors, and psychosocial characteristics and behaviors. Specific aims of this proposal are: Aim 1: To evaluate the influence of physical activity, defined by level of exercise, on incident and progressive early knee OA, expecting greater participation in light and moderate exercise to be protective; while greater participation in strenuous exercise will be deleterious. Aim 2: To investigate the influence of cardiovascular risk factors on knee OA anticipating that it may be an atheromatous disease. Aim 3: To examine the impact of psychosocial risk factors (e.g. pain coping strategies, self-efficacy, and social support) on knee OA. The Osteoarthritis Initiative (OAI) is an ideal setting in which to perform this proposed study, a publicly available observational study where 3284 were enrolled into the Incidence Cohort, a group selected to be at high risk for symptomatic knee OA. Participants attended 5 annual visits for comprehensive questionnaires, physical assessments, and standardized knee X-rays. Currently in the continuation phase, participants continue to have in-person encounters every 2 years allowing the opportunity to request additional survey information not included as part of the parent study. As a co-investigator of an ongoing ancillary study to the OAI and a researcher who has published 2 studies as lead author using OAI data, I am familiar with the design and conduct of the parent study to this proposed ancillary study. Therefore, I am optimally positioned to execute this proposed study that will potentially identify novel modifiable risk factors while contributing new data to enrich this already outstanding publicly available resource. I am a rheumatologist with a firm career goal to establish myself as an independent academic investigator with expertise in clinical OA research. By expanding my research interest from studying imaging-based determinants in knee OA to a broader approach including other clinical and patient-based factors, I will be able to study this disease comprehensively and more likely to identify risk factors that are indeed modifiable. To facilitate this goal, I plan to obtain formal training in survey methods, behavioral interventions, and research design, analysis and statistical methods related to behavior science research. This award will allow me to further expand my knowledge and skills, so that I will be able to establish a scientifically robust clinical research program and secure independent funding to sustain my research and mentor others. PUBLIC HEALTH RELEVANCE: The proposed study will evaluate 3 domains of potentially modifiable risk factors that may contribute to the development and worsening of knee osteoarthritis include: physical activity, cardiovascular risk factors (e.g. diabetes, high blood pressure, prior history of heart attack), and psychosocial characteristics and behaviors (e.g. coping strategies, self-efficacy, and social support). Because knee osteoarthritis is so common, occurring in at least 30% of those over the age of 60, and is one of the most debilitating diseases, if any modifiable risk factor can be identified that can prevent or slow the progression of this disease it could have substantial public health implications.